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A Study to Evaluate Enfortumab Vedotin in Subjects With Previously Treated Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)

Status
Active
Cancer Type
Breast Cancer
Esophogeal Cancer
Head and Neck Cancer
Stomach/ Gastric Cancer
Trial Phase
Phase II
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCT ID
NCT04225117
Protocol IDs
7465-CL-202 (primary)
NCI-2020-02645
Study Sponsor
Astellas Pharma Global Development, Inc.

Summary

The primary purpose of this study is to determine the antitumor activity of enfortumab
vedotin as measured by confirmed objective response rate (ORR).

This study will also assess other measures of antitumor activity; overall survival (OS); as
well as the safety and tolerability of enfortumab vedotin.

Objectives

This study will consist of 3 periods: screening/baseline, treatment and follow-up.

Screening/baseline period will take place up to 28 days prior to the first dose of study
treatment.

In the treatment period, starting at cycle 1, participants will receive enfortumab vedotin on
days 1, 8, and 15 every 28-day cycle until one of the treatment discontinuation criteria are
met. Disease assessment will be performed at screening/baseline and repeated every 8 weeks
(56 days ± 7 days) from the first dose of study treatment throughout the study until the
participant has radiologically confirmed disease progression, initiates a new subsequent
anticancer therapy, dies, withdraws consent, is lost to follow-up or the study closes,
whichever occurs first.

Participants who discontinue study treatment for reasons other than radiologically-confirmed
disease progression by RECIST Version 1.1 will enter into a post treatment follow-up period
and continue to receive imaging scans every 8 weeks (56 days ± 7 days) until the subject has
radiologically confirmed disease progression, initiates a new anticancer therapy, dies,
withdraws consent, is lost to follow-up or the study closes, whichever occurs first.

After 1 year on study treatment, the frequency of disease assessment will be reduced to every
12 weeks (84 days ± 7 days).

After radiologically-confirmed disease progression or initiation of subsequent anticancer
therapy, whichever occurs first, participants will be contacted every 12 weeks in the
long-term follow-up period for survival status until death, withdrawal of consent, lost to
follow-up or study closure, whichever occurs first.

Eligibility

  1. Subject is considered an adult according to local regulation at the time of signing the informed consent form (ICF).
  2. Subject has measurable disease by RECIST Version 1.1.
  3. Subject has accessible archival tumor tissue from either the primary tumor or a metastatic site, for which source and availability have been confirmed prior to study treatment. If no archival tumor tissue is available, the subject will have a biopsy to obtain tumor tissue prior to study treatment. If the subject is unable to undergo a biopsy due to safety concerns, enrollment into the study must be discussed with the medical monitor.
  4. Subject has ECOG performance status of 0 or 1.
  5. Subject has the following baseline laboratory data. If a subject has received a recent blood transfusion, the hematology tests must be obtained = 28 days after any blood transfusion.
  6. absolute neutrophil count (ANC) = 1.0 × 10^9/L
  7. platelet count = 100 × 10^9/L
  8. hemoglobin = 9 g/dL
  9. serum total bilirubin = 1.5 × upper limit of normal (ULN) or = 3 × ULN for subjects with Gilbert's disease
  10. creatinine clearance (CrCl) = 30 mL/min as estimated per institutional standards or as measured by 24-hour urine collection (glomerular filtration rate [GFR] can also be used instead of CrCl).
  11. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 × ULN
  12. Subject agrees not to participate in another interventional study while receiving study treatment in the present study.
  13. Additional contraceptive requirements exist for male and female subjects. Disease Specific Inclusion Criteria:
  14. Evidence of progression on or after the last regimen received.
  15. Locally advanced or metastatic disease that is not amenable to curative intent treatment. Cohort 1: HR+/HER2- breast cancer
  16. Subject has evidence of radiographic progression on or after the last regimen received.
  17. Subject has histologically- or cytologically-confirmed HR+/HER2- (estrogen receptor [ER] positive and/or progesterone receptor [PR] positive, and HER2 negative) breast cancers and are not considered a candidate for further hormonal therapy. Subject will be considered HR+ if biopsies show = 1% expression of ER or PR as per current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.
  18. Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
  19. Subject must have received a taxane or anthracycline in the neoadjuvant, adjuvant or incurable, locally advanced or metastatic setting.
  20. Prior cytotoxic regimen received in the neoadjuvant or adjuvant setting will count as a prior cytotoxic regimen if disease recurrence occurred during or within 6 months of completing the regimen.
  21. Subject has progressed, relapsed, or discontinued for toxicity during or after at least 1 prior standard of care cytotoxic regimen in the incurable, unresectable locally advanced or metastatic setting, and has not received > 2 prior lines of cytotoxic therapy in the locally advanced or metastatic setting. No limit applies to endocrine therapies. Poly(ADP-ribose) polymerases (PARP) inhibitors do not count as a line of cytotoxic therapy.
  22. Subject has progressed, relapsed, or discontinued for toxicity during or after receiving endocrine therapy or with hormonally-directed therapy with cyclin-dependent kinase (CDK) inhibitors. Prior therapy with CDK inhibitors is not required. Cohort 2: triple negative breast cancer (TNBC)
  23. Subject has evidence of radiographic progression on or after the last regimen received.
  24. Subject has histologically- or cytologically-confirmed TNBC; defined as unequivocal TNBC histology (ER-negative/PR-negative/HER2-negative). This is defined by < 1% expression of ER and PR by immunohistochemistry (IHC), and that are, for HER2, either 0 to 1+ by IHC, or IHC 2+ and fluorescence in situ hybridization (FISH) negative (not amplified) as per current ASCO/CAP guidelines.
  25. Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
  26. Subject must have received a taxane or anthracycline in the neoadjuvant, adjuvant or incurable, locally advanced or metastatic setting.
  27. Prior cytotoxic regimen received in the neoadjuvant or adjuvant setting will count as a prior cytotoxic regimen if disease recurrence occurred during or within 6 months of completing the regimen.
  28. Subject has progressed, relapsed, or discontinued for toxicity during or after at least 1 prior standard of care cytotoxic regimen in the incurable, unresectable locally advanced or metastatic setting, and has not received > 2 prior lines of cytotoxic therapy in the locally advanced or metastatic setting. Poly(ADP-ribose) polymerases (PARP) inhibitors do not count as a line of cytotoxic therapy.
  29. Subject has received prior therapy with an anti-programmed cell death protein-1 (PD-1) or an anti-programmed cell death-ligand 1 (PD-L1) based on subject's tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed or discontinued treatment due to toxicity, or therapy is contraindicated for subject. Cohort 3: squamous non-small cell lung cancer (NSCLC)
  30. Subject has evidence of radiographic progression on or after the last regimen received.
  31. Subject has histologically or cytologically-confirmed squamous NSCLC.
  32. Subjects with mixed histology NSCLC are eligible provided there is not any component of neuroendocrine histology.
  33. Subjects with known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species (ROS), BRAF, or other actionable mutations are eligible if treated with mutation targeted therapy and have progressed, relapsed, or discontinued treatment due to toxicity.
  34. Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
  35. Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1 platinum-based standard of care regimen for locally advanced or metastatic disease, and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally advanced or metastatic setting.
  36. Subjects with locally advanced disease who previously received curative intent treatment with platinum-based standard of care regimen in the adjuvant or neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible if they have progressed or relapsed within 6 months of completion.
  37. Maintenance therapy does not constitute a new chemotherapy regimen provided there was no progression after the initial platinum-based regimen.
  38. Changing chemotherapy agents during platinum-based treatment for the management of toxicities does not constitute a new chemotherapy regimen provided no progression had occurred while on the initial therapy.
  39. Subject has received prior therapy with an anti-programmed cell death protein-1 (PD-1) or anti-programmed cell death-ligand 1 (PD-L1) based on subject's tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed, relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for subject. Cohort 4: non-squamous non-small cell lung cancer
  40. Subject has evidence of radiographic progression on or after the last regimen received.
  41. Subject has histologically- or cytologically-confirmed non-squamous NSCLC.
  42. Subjects with mixed histology NSCLC are eligible provided there is not any component of neuroendocrine histology.
  43. Subjects with known EGFR, ALK, ROS, BRAF, or other actionable mutations are eligible if treated with mutation targeted therapy and have progressed, relapsed, or discontinued treatment due to toxicity.
  44. Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
  45. Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1 platinum-based standard of care regimen for locally advanced or metastatic disease, and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally advanced or metastatic setting.
  46. Subjects with locally advanced disease who previously received curative intent treatment with platinum-based standard of care regimen in the adjuvant or neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible if they have progressed or relapsed within 6 months of completion.
  47. Maintenance therapy does not constitute a new chemotherapy regimen provided there was no progression after the initial platinum-based regimen.
  48. Changing chemotherapy agents during platinum-based treatment for the management of toxicities does not constitute a new chemotherapy regimen provided no progression has occurred while on the initial therapy.
  49. Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed, relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for subject. Cohort 5: head and neck cancer
  50. Subject has evidence of radiographic progression on or after the last regimen received.
  51. Subject has histologically- or cytologically-confirmed head and neck cancer.
  52. Primary tumor site must arise from the oral cavity, oropharynx, hypopharynx, and larynx; tumors arising from the nasopharynx are excluded. Salivary gland tumors and/or parotid gland tumors are not eligible for Cohort 5.
  53. Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
  54. Subject has progressed, relapsed, or discontinued treatment due to toxicity after 1 platinum-based standard of care regimen for locally advanced or metastatic disease, and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally advanced or metastatic setting.
  55. Subjects with locally advanced disease who previously received curative intent treatment with platinum-based standard of care regimen in the adjuvant or neoadjuvant setting or as part of concomitant chemoradiation therapy are eligible if they have progressed or relapsed within 6 months after completion.
  56. Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed, relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for subject. Cohorts 6, 7 and 8: gastric or gastroesophageal junction (GEJ) or esophageal adenocarcinoma
  57. Subject has evidence of radiographic progression on or after the last regimen received.
  58. Subject has histologically- or cytologically-confirmed gastric, GEJ, or esophageal cancer.
  59. Subject has locally advanced or metastatic disease that is not amenable to curative intent treatment.
  60. Subject has progressed, relapsed, or discontinued due to toxicity after 1 platinum-based standard of care regimen for locally advanced or metastatic disease, and has not received > 2 prior lines of cytotoxic anticancer therapy in the locally advanced or metastatic setting.
  61. Neoadjuvant or adjuvant cytotoxic regimens will count as a prior regimen if relapsed or progressed = 6 months after completion.
  62. Subject must have received a HER2 directed therapy if known to have HER2 positive cancer.
  63. Subject has received prior therapy with an anti-PD-1 or anti-PD-L1 based on subject's tumor PD-1 or PD-L1 expression and local treatment guidelines and has progressed, relapsed, or discontinued treatment due to toxicity, or therapy is contraindicated for subject.
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